The proposed research concerns our interest in the genetic control of immunoglobulin synthesis. Recent studies have suggested that genetic variants of immunoglobulins are encoded by groups of linked, rather than allelic, structural genes. This concept arose from a number of independent findings that occasional animals exhibit serum Ig molecules with the worn allotype; these are referred to as latent allotypes. The correct allotypes based on genetic and quantitative typing are referred to as nominal allotypes. This proposal seeks to analyze further several features of the latent allotype phenomenon, particularly controls that may be exerted at the cell level. The main thrust of this application centers on the hypothesis that the expression of latent allotype is governed by mechanisms similar to those operating in the phenomena of allotype suppression and its reversal. Our working hypothesis considers the possibility that animals normally contain low levels of B-cells with a commitment for the latent allotype and that such cells are held in a state of dormancy by latent allotypes specific suppressor cells. Preliminary experiments with splenocyte cultures have shown that release of suppression can be achieved by modulation with anti-allotypic antiserum. We propose to examine the factors responsible for this modulating effect, characterize the putative suppressor cell and develop rabbit-mouse hybridoma cell lines that synthesize rabbit Ig with a latent allotypic marker. Our overall objective is to study rabbit immunoglobulin allotypes as aids in monitoring the genetics and evolution of immunoglobulins in general. In recent years, evidence for the genetic control of immune responses to a variety of antigens, including resistance and susceptibility to disease, has added new dimensions to the immune process. It is possible that similar genetic processes are operable in a variety of genetic deficiency diseases, autoimmune and other degenerate diseases, transplantation reactions, etc.